The overall goal of this study is to determine the biological significance of a sub-optimal anti-tumor immune response. The role of the immune system in regulating tumor growth has been controversial since the demonstration that tumors carry neoantigens recognizable by the host. This controversy is particularly active with respect to the autochthonous or primary-tumor-bearing host. It seems appropriate, therefore, to study the influence of the immune system on tumor induction and progression in the primary host, along with the progression of neoplasms from benign to malignant, using a tumor transplantation system. Immunomanipulated mice will be used to determine whether a weak, but specifically directed, anti-tumor response will induce a higher than normal probability of tumor development over that seen in mice with an immune responsiveness that is either much stronger or essentially absent. The tumors induced in these experiments will then be tested to determine whether the immunologic status of the host was able to modify the tumor's immunogenicity. Preliminary results have documented that animals with a suboptimal immune capacity developed more skin tumors with shorter latent periods than those animals with either a greater of lesser immune capacity. If the immune system can stimulate as well as inhibit the induction and progression of neoplasia, the need for defining the biological boundaries of these effects becomes essential for development of effective immunotherapy protocols.